Role for Bcl-xL as an inhibitor of cytosolic cytochrome C accumulation in DNA damage-induced apoptosis
S Kharbanda, P Pandey, L Schofield… - Proceedings of the …, 1997 - National Acad Sciences
Proceedings of the National Academy of Sciences, 1997•National Acad Sciences
Cytochrome C is a mitochondrial protein that induces apoptosis when released into the
cytosol or when added to cell-free extracts. Here we show that cells that overexpress the Bcl-
2-related protein Bcl-xL fail to accumulate cytosolic cytochrome C or undergo apoptosis in
response to genotoxic stress. Coimmunoprecipitation studies demonstrate that Bcl-xL
associates with cytochrome C. Cytochrome C binds directly and specifically to Bcl-xL and
not to the proapoptotic Bcl-xs protein. The results also demonstrate that Bcl-xs blocks …
cytosol or when added to cell-free extracts. Here we show that cells that overexpress the Bcl-
2-related protein Bcl-xL fail to accumulate cytosolic cytochrome C or undergo apoptosis in
response to genotoxic stress. Coimmunoprecipitation studies demonstrate that Bcl-xL
associates with cytochrome C. Cytochrome C binds directly and specifically to Bcl-xL and
not to the proapoptotic Bcl-xs protein. The results also demonstrate that Bcl-xs blocks …
Cytochrome C is a mitochondrial protein that induces apoptosis when released into the cytosol or when added to cell-free extracts. Here we show that cells that overexpress the Bcl-2-related protein Bcl-xL fail to accumulate cytosolic cytochrome C or undergo apoptosis in response to genotoxic stress. Coimmunoprecipitation studies demonstrate that Bcl-xL associates with cytochrome C. Cytochrome C binds directly and specifically to Bcl-xL and not to the proapoptotic Bcl-xs protein. The results also demonstrate that Bcl-xs blocks binding of cytochrome C to Bcl-xL. Our findings support a role for Bcl-xL in protecting cells from apoptosis by inhibiting the availability of cytochrome C in the cytosol.
National Acad Sciences
